New technique can remove nanoparticles unaltered from blood with ease.

Expanded use of engineered nanoparticles in consumer products and drug delivery increases the potential for environmental release, overexposure or unintended biological exposure. As a result, extraction techniques with integrated measurement capabilities are needed to accurately and safely extract samples to quantify nanoparticle size, mass, and particle number distributions in biological matrices. However, removing nanoparticle by-type from biological substrates has proven difficult, in that surface chemistry is altered, making measurements inaccurate; or the removal has proven impossible.

Therefore, there is an urgent need for the development of standardized procedures for extracting, characterizing and quantifying nanoparticles. Now, researchers at the University of California, San Diego state they have developed a new technology that uses an oscillating electric field to easily and quickly isolate drug-delivery nanoparticles from the blood. The team state that the technology could serve as a general tool to separate and recover nanoparticles from other complex fluids for medical, environmental, and industrial applications. The study is published in the journal Small.

Previous studies show that nanoparticles are difficult to separate from plasma, the liquid component of blood, due to their small size and low density. Traditional methods to remove nanoparticles from plasma samples typically involve diluting the plasma, adding a high concentration sugar solution to the plasma and spinning it in a centrifuge, or attaching a targeting agent to the surface of the nanoparticles. These methods either alter the normal behaviour of the nanoparticles or cannot be applied to some of the most common nanoparticle types. Therefore, the group were interested in a fast and easy way to take nanoparticles out of plasma to analyse a non-disrupted surface chemistry, to redesign them to work more effectively in blood. The current study is the first example of isolating a wide range of nanoparticles out of plasma with a minimum amount of manipulation with the technique able to be used to recover nanoparticles in a lot of different processes.

The current study used a chip that can work in the high salt concentration of blood plasma, the chip’s ability to pull the nanoparticles out of plasma is based on differences in the material properties between the nanoparticles and plasma components. Results show that when the chip’s electrodes apply an oscillating electric field, the positive and negative charges inside the nanoparticles reorient themselves at a different speed than the charges in the surrounding plasma; this momentary imbalance in the charges creates an attractive force between the nanoparticles and the electrodes. Data findings show that as the electric field oscillates, the nanoparticles are continually pulled towards the electrodes, leaving the rest of the plasma behind.

The lab explain that the chip contains hundreds of tiny electrodes that generate a rapidly oscillating electric field that selectively pulls the nanoparticles out of a plasma sample. The group observed that when a drop of plasma spiked with nanoparticles was inserted into the electric chip, nanoparticle recovery occurred within 7 minutes without any modifications to the plasma samples or to the nanoparticles. They go on to state that the technology worked on different types of drug-delivery nanoparticles that are typically studied in various labs.

The team surmise that this new nanoparticle separation technology will enable researchers to better monitor what happens to nanoparticles circulating in a patient’s bloodstream. For the future, the researchers state that their technology could be used to determine if the blood chemistry of a specific patient is compatible with the surfaces of certain drug-delivery nanoparticles.

An artist’s representation of the nanoparticle removal chip developed by researchers in Professor Michael Heller’s lab at the UC San Diego Jacobs School of Engineering. An oscillating electric field (purple arcs) separates drug-delivery nanoparticles (yellow spheres) from blood (red spheres) and pulls them towards rings surrounding the chip’s electrodes. The image is featured as the inside cover of the Oct. 14 issue of the journal Small. Credit: Stuart Ibsen and Steven Ibsen.